Summary of the Fifth Annual Public Interest
Organization Meeting

February 11, 2004 - Bethesda, Maryland

Summary Report

The National Heart, Lung, and Blood Institute (NHLBI) convened its fifth annual public interest organization (PIO) meeting to encourage and promote public input and involvement in Institute activities. Approximately 130 individuals participated in the 1-day meeting. They included members of more than 65 public interest organizations, as well as representatives from professional societies, voluntary health agencies, the NHLBI, and the National Heart, Lung, and Blood Advisory Council (NHLBAC). The agenda and format for the meeting were designed to foster interaction among all the individuals and organizations attending. The four previous PIO meetings were held

Two main themes for the fifth annual meeting were fostering collaborations and sharing best practices. The agenda included:
  • Remarks by the Director, National Institutes of Health (NIH), on the NIH Roadmap
  • Presentations describing a public advisory roundtable and PIO participation in research
  • Facilitated discussions of collaborations involving NHLBI and PIOs in three areas
  • Scientific tutorials—presentations on cutting-edge topics, followed by question-and-answer periods
  • A research presentation on sleep and its disorders
  • Roundtables for PIOs to share best practices and lessons learned in six areas.
The meeting was organized to encourage interaction among all participants and discussion of activities and topics germane to PIOs. Participants contributed to the separate, facilitated discussions of collaborations in:
  • Disseminating public information
  • Helping patients
  • Promoting relevant research.
During the roundtable on sharing best practices, PIOs exchanged ideas and expanded on lessons learned through:
  • Developing materials for patients and the public
  • Fundraising
  • Organizing a scientific advisory board
  • Putting a face on disease
  • Starting a disease registry and mobilizing patient participation in research studies
  • Starting and sustaining support groups.
This report summarizes the presentations and discussions at the meeting.

Introductory Remarks

Dr. Barbara Alving, Acting Director, NHLBI, welcomed everyone to the meeting. She noted that participation in the annual PIO meetings has increased every year—evidence of their success. The meetings were initiated under the leadership of the former Director, NHLBI, Dr. Claude Lenfant, who stepped down from his position in September 2003 to pursue interests in international health. Dr. Alving commented that the agenda for the fifth meeting was organized to facilitate exploration of ways for PIOs to collaborate with each other toward achieving their common goals. She invited the representatives of organizations attending to share their expertise with other PIOs, and she encouraged everyone to give feedback about the meeting to the NHLBI.

Dr. Alving remarked that February is “American Heart Month” and that February 6 was National Wear Red Day, a part of The Heart Truth campaign to increase awareness about women and heart disease. The campaign is sponsored by the NHLBI in partnership with the Office on Women’s Health of the U.S. Department of Health and Human Services, the American Heart Association, WomenHeart: the National Coalition for Women with Heart Disease, and others. Dr. Alving noted that the symbol of the campaign is a red dress, and she added that both men and women were wearing their red dress pins.

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Overview of the NIH Roadmap

Dr. Elias Zerhouni, Director, NIH, discussed the themes and initiatives of the NIH Roadmap in the context of trends in disease and research. He emphasized that the PIOs have an important role in supporting the NIH mission, and he thanked the PIOs for their continued advice and wisdom. Dr. Zerhouni noted that approximately 21,000 individuals give advice to the NIH each year through peer review panels and advisory committees and that these individuals “drive NIH’s energy” and are an essential “reality check” for the agency.

The NIH consists of 27 institutes and centers (ICs). It has experienced rapid growth, with a doubling of its budget in 5 years, and is challenged by an even greater expansion in the complexity of scientific and research issues. In this new era, key questions for the NIH are:

  • What is the state of science?
  • What are the challenges?
  • What are the roadblocks?
  • How can the NIH deploy its resources and organize better to overcome roadblocks and pursue challenges?
Dr. Zerhouni noted that much attention is being given to achieving a balance between conducting basic research and translating research findings into practice. He compared the interconnected wholeness of basic and translational research to a hand—with the palm representing basic research and the fingers representing translational research—and he noted that the need to balance these endeavors reflects the changing landscape of disease and research over the past 30 years.

From a public health perspective, the focus shifted over that same period from acute disease to chronic disease. In heart disease and cancer, for example, scientists have made great progress in preventing and treating acute events (e.g., stroke). While these advances have increased life expectancy, they also have led to the emergence of chronic conditions (e.g., congestive heart failure) that diminish quality of life. Other problems that require attention include health disparities, the health effects of aging, and disabling conditions such as musculoskeletal disease.

From a research perspective, scientists now have tools and techniques for exploring complex biological systems in ways not possible 30 years—or even 5 years—ago. With the completed sequencing of the human genome in 2003 and the emergence of high-throughput computer capabilities for analyzing tissue and generating biological data, scientists can now rapidly identify genes associated with a disease and probe questions about their function. Through this research, for example, we now know that cancer is not caused by a “magic bullet,” as was thought in 1973, but is the result of complex interactions involving many, many genes and environmental factors as well.

Dr. Zerhouni noted that, with these perspectives in mind, the NIH launched in September 2003 the NIH Roadmap. The NIH views the Roadmap as an investment portfolio to transform medical research and to speed the translation of research findings into clinical practice. In fiscal year 2004, NIH is allocating approximately 0.05-0.06 percent of its budget to the Roadmap. Its three major themes are:

  • New Pathways to Discovery: New Approaches and Technologies
  • Multidisciplinary Research Teams of the Future
  • Re-engineering the Clinical Research Enterprise.
Within these themes, the NIH is pursuing 28 scientific initiatives. Dr. Zerhouni elaborated on several of them. He noted that two phenomena underpin the new pathways to discovery—the complexity of biological systems and the convergence between biological fields. To foster multidisciplinary collaborations, the NIH is investing in quantitative research, development of specific tools (e.g., molecular probes) for measuring effects on biological systems, production of molecular libraries that will be publicly available, and other related efforts. Ultimately, these bold, high-risk initiatives will enable researchers to use computational programs to search for biological interactions.

The NIH also is encouraging coordination of integrated, multidisciplinary research teams to test bold ideas and to solve problems in unexplored areas of research. One initiative under this theme is the NIH Director’s Pioneer Award, a 5-year grant for investigators who are exceptionally creative and diligent and who are pursuing bold research relevant to the NIH mission. All ICs are contributing funds to this award program.

Dr. Zerhouni noted that the obvious need to re-engineer the clinical research enterprise arises from a number of problems, which include the:

  • Burden of regulations affecting clinical research
  • Complexity of clinical research
  • Decreasing number of clinical scientists (only 2 percent of physicians in academia are clinical scientists)
  • Lack of standardized terminology and definitions for recording clinical data
  • Inefficient, fragmented health care and insurance system
  • Low participation of patients in clinical trials.

He noted that the problems are not insurmountable and that the NIH and PIOs can provide leadership to resolve them. Dr. Zerhouni emphasized that clinical research is ultimately driven by partnerships between researchers and patients, including patient advocacy groups. To tackle major health problems, the United States must develop a more unified and integrated system of health care with patients at the center.

Complete details and progress on the NIH Roadmap are presented on the NIH Web site: www.nih.gov

Discussion

The participants congratulated Dr. Zerhouni on his efforts and thanked him for developing the NIH Roadmap.

Trans-NIH PIO

The participants asked Dr. Zerhouni to consider forming a trans-NIH PIO. Dr. Zerhouni indicated that he would present this suggestion to the NIH Director’s Council of Public Representatives (COPR), which he has already asked to be more integrative of public input. He commented that the NIH faces the same organizational problem as the PIOs—“silos vs. synergy.”

NIH Information on the Impact of PIOs on Research

The participants asked whether the NIH has a single locus of information on the impact of PIOs on research. Dr. Zerhouni responded that the NIH has no single site, although several ICs have addressed this topic. For example, the National Institute of Diabetes and Digestive and Kidney Diseases compiles information on self-care for diabetes, and the NHLBI Office of Prevention, Education, and Control supports educational programs for patients with asthma, chronic obstructive pulmonary disease (COPD), and other conditions. The PIOs can access this information on the Web sites of the individual NIH components (see www.nih.gov.)

Communities of Research

Dr. Zerhouni emphasized that creation of “communities of research” that integrate patients, patient advocacy groups, and academic health centers is an essential aspect of re-engineering the clinical research enterprise. He cited the success of the NIH’s longstanding collaboration with the cystic fibrosis community in extending the life expectancy of patients with cystic fibrosis, as an example of the gains to be made from communities of research. Through such communities, evidence-based research can lead to identification of best practices for improving treatment, while the search for possible causes and a potential cure continues. Dr. Zerhouni noted that the NIH collaboration in cystic fibrosis is a proven model for other communities of research that PIOs may wish to emulate.

Collaboration between PIOs and the NIH

Responding to a question about how PIOs can collaborate with the NIH to help ensure the success of research programs, Dr. Zerhouni encouraged the PIOs to help:

  • Stimulate and sustain community, scientific, and congressional interest in research opportunities
  • Increase support for research
  • Identify successful NIH pilot models of translational research.

Commenting on how the NIH could help match PIOs with promising researchers, Dr. Zerhouni encouraged the PIOs to peruse the CRISP database—a publicly available, searchable database of all federally supported biomedical research projects. CRISP stands for “Computer Retrieval of Information on Scientific Projects.” The database can be accessed through the NIH Web site or directly at CRISP

NIH Research on Rare Diseases

The participants thanked Dr. Zerhouni for NIH support of research on rare diseases, saying that it was like “being Cinderella with the glass slipper at the NIH ball.” Dr. Zerhouni noted that the NIH is very focused on rare diseases and that this research is a “driver” for the NIH initiative to develop molecular probes. He also noted that research on rare diseases is a unique feature of the NIH intramural research program, and he applauded the efforts of the NIH Office of Rare Diseases.

Commenting on the need to promote research on the relationship between lung and airway diseases and other diseases, Dr. Alving noted that the NHLBI is developing an initiative to foster collaboration among NIH components in research on lung diseases as they affect other organ systems.

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The NHLBI as a Catalyst for Public Involvement

Dr. William Martin, former President, American Thoracic Society (ATS), and two members of the ATS Public Advisory Roundtable (PAR) described the origin, activities, and current challenges for the ATS-PAR. Dr. Martin suggested that the ATS-PAR offers a model for increasing the influence and effectiveness of the PIOs within the medical research system. He noted that the PIOs are just beginning this venture and have the power to propel the system. The NHLBI serves as an important catalyst for this public involvement.

Origin of the ATS-PAR

Dr. Martin described the germination of his idea for a PAR, which began when he was a staff member of the U.S. Senate Labor and Human Resources Committee. At the time, the committee was responsible for many aspects of health care reform, including reauthorization of the NIH. Subsequently, Dr. Martin became a member of the NHLBAC and then President, ATS. These experiences convinced him of the power of patient advocacy groups on Capitol Hill and the necessity for the ATS to seize a moment of opportunity to involve PIOs in its efforts. The ATS is a membership organization representing approximately 12,000 physicians and scientists.

Dr. Martin emphasized that:

  • PIOs have a powerful message to communicate—treatments are needed today, not tomorrow.
  • Their perspective is important and unique.
  • Only PIOs have the passion to communicate and advocate this message with clarity.

Under his leadership, the ATS board of directors approved the concept of a PAR in December 2000. The ATS-PAR convened an organizational gathering on January 31, 2001, in conjunction with the NHLBI’s second annual PIO meeting, and held its first meeting in March 2001 in conjunction with a meeting of the ATS board of directors. Approximately 35 PIOs related to respiratory diseases have expressed an interest in the ATS-PAR, and PIOs have embraced it with energy and enthusiasm.

Activities and Programs: Overview

Ms. Paula Yette Polite, President, Sarcoidosis Research Institute, served as the first chairperson of the ATS-PAR. She described its activities and programs.

In March 2001, the structure, mission, goals, and objectives of the ATS-PAR were defined at its first joint meeting with the ATS board of directors. Four PAR teams were established—advocacy, communication, education, and research. Their activities include the following:

  • Advocacy—1-day training in advocacy and congressional outreach
  • Communication—reporting of regional activities in ATS’ newsletter, compiling a list of organizations interested in lung diseases, maintaining a listserv, and hosting the ATS-PAR Web site ATS-PAR
  • Education—organizing an annual symposium, assembling educational materials, sponsoring continuing education credits for health care professionals
  • Research—coordinating a matching funds program to support research projects with the ATS.

Other ATS-PAR activities include an effort to address patient involvement in the ethical conduct of clinical trials, presentation of awards, outreach to other PIOs, and development of a strategic plan. Ms. Polite noted that ATS committees are represented on the ATS-PAR and that ATS-PAR representatives participate on major ATS committees. In 2003, the ATS-PAR received the ATS public service award and presented two awards, to Dr. Martin for public service and to the NHLBI for excellence.

Ms. Polite invited and encouraged all PIOs to:

  • Join the ATS-PAR listserv
  • articipate in the matching funds program to support research
  • Attend the 100th ATS International Conference, in Orlando, Florida, May 21-26, 2004
  • Develop similar umbrella organizations for PIOs that have related interests.
Challenges and Future Directions

Mr. John Walsh, President and Chief Executive Officer, Alpha-1 Foundation, conveyed the attributes of the ATS-PAR and highlighted some future directions. He noted that the ATS-PAR logo is a bridge, reflecting its objective of helping to build a bridge among patient communities and, in relation to the NHLBI, to build a bridge between scientists and patients. The ATS-PAR is highly synergistic; it is a true partnership with the ATS and is committed to expanding its representation to the entire lung and airway community.

Mr. Walsh noted that the NHLBI has been a catalyst for PIOs to work together and in collaboration with the NHLBI. Two seed projects in which the ATS-PAR is involved, with the encouragement of the NHLBI, are the:

  • COPD-ALERT—an Internet-based resource network that offers support and advocacy for patients, caregivers, and health care professionals. The ATS-PAR, the ATS, and other collaborating organizations endorsed a recently completed survey of patients and health care providers that provided definitive data on COPD.
  • COPD and Alpha-1 Education Days—the ATS-PAR is sponsoring an education day for patients and health care professionals at all COPD centers funded by the NHLBI.

Mr. Walsh reported that 40 representatives from 22 PIOs attended this year’s ATS-PAR meeting, held on February 10 before the PIO meeting. The main topic was strategic initiatives for the future. Two key initiatives are:

  • Building PARtnerships within the Community—the ATS-PAR is serving as a “foot soldier” for the NHLBI in Outreach 435, an effort to inform and educate all congressional districts about NHLBI activities.
  • Advocacy Call to Action—a specific call to revise airline regulations to allow for use of ambulatory supplemental oxygen on flights.
Mr. Walsh urged all PIOs to “take collaboration to the next level and meet the needs of our communities.” He thanked the NHLBI for being the catalyst for collaboration.

Discussion

Mr. Walsh asked the participants to suggest ideas for collaboration. They suggested the following.

Identify and Approach Other Professional and Scientific Organizations

Dr. Martin suggested that the ATS-PAR and the ATS could help PIOs develop strategies for approaching leading professional and umbrella organizations in the sciences. He also suggested that the ATS leadership could communicate with the leadership of other professional societies on behalf of the PIOs. He noted that two important aspects of developing a partnership relationship are trust and an alignment of interests, and he said that the PAR–ATS collaboration has added value to ATS.

Dr. Homer Boushey, Jr., President, ATS, elaborated on the value of PIOs to professional societies. Representing patients, the PIOs:

  • “Remind professional societies why they are there”
  • Often have international patient members and contacts
  • Contribute inspiring and humbling stories of patients at society meetings
  • Have the power to mobilize support for national policies
  • Nurture and support innovative, high-risk research
  • Can engage new and different scientists on a research topic.

For PIOs, collaborations with professional societies offer:

  • Connections with researchers, science faculty, and administrators in medical schools
  • Potential partnerships with primary care groups on education initiatives.

”Be at the Table”

The participants emphasized that the PIOs must be “part of the process.” PIOs must bring the perspectives of patients to national and local discussions of issues concerning health care and medical systems (e.g., insurance, access to care, academic research, medical education).

Create Grass-roots Networks

The participants suggested that the PIOs could “piggyback” national models of collaboration (e.g., COPD-ALERT) onto local efforts. They noted that templates for collaboration need to be developed and suggested that the PIOs could approach the NHLBI and the NIH Office of Rare Diseases for support of “incubator,” capacity-building projects.

Stay Unified in Outreach and Advocacy

The participants highlighted the importance of having a unified message locally, regionally, and nationally. The hemophilia community, for example, was able to stimulate and obtain passage of federal legislation through a 5-year campaign unified at local, regional, and national levels. “One letter and one voice can make a difference.”

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Facilitated Discussions

Following the morning presentations, the attendees had an opportunity to participate in one of three facilitated discussions held in separate breakout rooms. The theme was collaborations—in disseminating public information, helping patients, and promoting relevant research. Approximately 25-30 individuals attended each session, which was facilitated by NHLBI staff and PIO representatives. The discussions were interactive and thought-provoking. The topics and comments are summarized below.

Collaborations in Disseminating Public Information

Facilitators—
Dr. Robinson Fulwood, Public Health Program Development Manager, Office of Prevention, Education, and Control, NHLBI
Ms. Barbara Liu, Deputy Director, Office of Science and Technology, NHLBI
Ms. Virginia Ladd, President and Executive Director, American Autoimmune Related Diseases Association

The discussants addressed the reasons to collaborate (or not), how to work with other PIOs, and strategies for disseminating public information.

Reasons to Collaborate

Ms. Ladd provided a handout on this topic. By collaborating with other PIOs and organizations, a PIO can:

  • Avoid duplication of effort and save time and resources
  • Amplify its "voice" so that it is not lost among others wanting to be heard
  • Enhance its reputation and visibility
  • Learn about other approaches and resources
  • Give and receive help.

A PIO may choose not to collaborate if:

  • The potential collaboration will not fit with its mission and priorities
  • The PIO does not have or want to take the time needed to build the collaboration
  • The potential partner does not have the same ethical standards
  • The potential partner does not understand how a nonprofit organization, a government agency, or a corporation works
  • The other parties are not as enthusiastic as the PIO about the collaboration.

How to Work With Other PIOs

To work with others, a PIO will want to:

  • Clearly communicate its values, goals, and objectives—before and during collaboration
  • Approach potential collaborators in a strategic way—for example, invite all interested groups to one large meeting, to save time and resources
  • Avoid competition—by identifying and working together on common goals, being willing to give up ownership of issues or projects, and focusing on shared passions to help patients
  • Peruse available resources on collaboration.

PIOs may choose partners that are not advocating for the same disease or disorder, but for related conditions (e.g., lymphedema and cancer). Competition, which is a barrier to effective collaboration, may arise when different organizations are focused on the same disease.

A helpful resource for learning how to form coalitions is the Allies Against Asthma's coalition connections Web site: Asthma Coalitions.

Strategies for Disseminating Public Information

When making plans to disseminate public information, PIOs need to identify all of the resources potentially available for helping with outreach. Four interrelated strategies are:

  • Find a spokesperson to raise awareness about your PIO
  • Engage the media in getting your message out
  • Identify and approach potential sponsors
  • Know your constituency.

Celebrities and patients constitute good public spokespersons. PIOs can collaborate in having the same spokesperson. Celebrity spokespersons can give instant public credibility and visibility to a cause. Some celebrities may be reluctant to participate, may not convey the message exactly as intended, or may expect payment for their services, which could weaken their public credibility.

PIOs that are interested in finding a celebrity spokesperson could:

  • Identify celebrities with the condition represented by the PIO or a related disorder
  • Look for lists of celebrities who are interested in volunteering
  • Ask celebrities to appear at an event or on a game show (e.g., Wheel of Fortune) in order to raise money for the organization.

Patients who are spokespersons help to “put a face” on a disease and are very moving and credible when they share their experiences. A good public relations firm (many of them are inexpensive) can help a PIO leader or patient develop the skills needed to ba an effective spokesperson.

To engage the media (the press, local radio, and television stations) in its cause, a PIO can:

  • Form alliances with the media to let them know that the PIO has the latest research information on a disease—the media will then come to the PIO for quotes and input
  • Work with local radio stations to construct a public service announcement (PSA) that presents the PIO’s message.

Corporate sponsors can help to defray costs and enable PIOs to reach a broader audience. (One PIO leader, for example, asked a company to donate popcorn for a booth at a health fair. While distributing the popcorn, the PIO asked recipients to complete a short survey.)

For PIOs to be effective, they must know the audience(s) they are trying to reach and identify methods most likely to be effective for this audience. PIOs should assess the needs of their constituencies before designing any information to be disseminated—not all communities have the same needs or consume information in the same way.

Some strategies for knowing and reaching your constituency are:

  • Go where your audience is (e.g., in homes, churches, beauty salons, other community places).
  • Spend time at malls and county fairs to reach large numbers of people
  • Make your message culturally sensitive and appropriate for the specific populations
  • Work with a leader in the community you are trying to reach.

Collaborations in Helping Patients

Facilitators—
Ms. Paula Blonski, Vice President, ARDS Foundation
Ms. Eleanor Schron, Nurse Scientist, Clinical Trials Scientific Research Group, NHLBI
Ms. Nancy Loving, Executive Director, WomenHeart: the National Coalition for Women with Heart Disease

The discussants focused on the following six ways that PIOs can collaborate to help their patients:
  • Work with the media
  • Serve as resources for health care providers
  • Facilitate prayer and support
  • Meet patients’ diverse needs
  • Maintain a viable and successful organization
  • Identify available resources.

Working with the Media

Patients benefit from telling their stories, but most need some training before they can be effective spokespersons. PIOs can partner with public relations firms and offices that provide this training. Firms have been willing to donate their services as pro bono activities for nonprofit organizations. Public relations offices in community hospitals have provided media training for PIO members and, in exchange, the members appear in film clips featuring hospital activities and speak about health promotion events. Through such collaborations, PIOs can develop relationships with health reporters. PIOs should not hesitate to ask, or even beg, for help.

Serving as a Resource for Health Care Providers

Many health professionals are more willing to talk with medical colleagues than with patients whom they have never met. PIOs can establish doctor-to-doctor telephone lines for physicians to exchange opinions or receive advice from other physicians who are experts on the particular disease or condition. Serving as a resource for other health professionals can be one of the major responsibilities of a PIO's medical board members.

Facilitating Prayer and Support

Illness affects a patient’s emotional and spiritual health, as well as his or her physical health. PIOs can establish prayer networks and e-mail exchanges to help their members give support to each other. Many patients and families are comforted when other PIO members reach out to them or pray for them. However, PIOs should recognize that some patients and families are not comfortable being contacted by strangers or receiving prayers from people of a different faith.

Meeting Patients’ Diverse Needs

PIOs have used a variety of approaches to meet the diverse needs of patients. For example, some patients may not be fluent in English, some may be blind, and others may not be able to access the Internet. Some ideas are:

  • Enlist the help of local chapters of national clubs (e.g., Portuguese-American, Dutch-American) to translate PIO materials into different languages.
  • Partner with state chapters of the Society for the Blind to record printed materials on tape.
  • Ask other organizations and professionals to help—a local YWCA may agree to display health materials for women; the annual church festival may allow a booth for health screenings and dissemination of materials; physicians, nurses, and other health care professionals (e.g., respiratory therapists) may refer patients to your PIO.

Maintaining a Viable and Successful Organization

Each PIO should focus on what it can do best, which may be:

  • Promoting health care reform
  • Hosting support groups
  • Visiting patients
  • Educating patients, health care providers, or the public
  • Helping patients with reimbursement issues.

It takes a strong leader to recognize that a PIO cannot do everything and must prioritize what it wants to accomplish. A PIO’s budget often drives its priorities.

To decide on its focus and priorities, a PIO may want to:

  • Ask a for-profit company to donate pro bono staff time to help develop a strategic plan
  • Invite a business school to provide assistance
  • Hold a weekend workshop for its members.

With a focus and priorities, PIO members will be eager to return to their communities and raise money for the PIO.

Identifying Available Resources

Sometimes it is not necessary to create a new PIO. Establishing a nonprofit organization is a complex and difficult undertaking. Patients and families might benefit by partnering with an existing entity or entities for the services they need.

One PIO representative recommended the Self-Help Group Sourcebook C Your Guide to Community and Online Support Groups(7th ed.), compiled and edited by Barbara J. White and Edward J. Madara, American Self-Help Group Clearinghouse, Saint Clare's Health Services, Denville, New Jersey. Associated with this sourcebook is a searchable database of support groups and other resources Selfhelp.

Collaborations in Promoting Relevant Research

Facilitators—
Dr. Charles Peterson, Director, Division of Blood Diseases and Resources, NHLBI
Dr. William Martin, former President, American Thoracic Society
Dr. John Walsh, President and CEO, Alpha-1 Foundation

The facilitators drew on their experiences to emphasize the important roles that PIOs have in promoting relevant research. For example, PIOs can:
  • Challenge the government to confront specific disease issues
  • Help to sustain the pipeline of researchers for the next generation
  • Match researchers with diseases that need attention
  • Advocate for patients and focus research on patient needs
  • Inform researchers about other relevant ongoing projects
  • Build a bridge to professional societies
  • Support research with matching funds
  • Learn from other PIOs and about related diseases and conditions
  • Contribute important perspectives at scientific conferences and workshops.

The discussants addressed ways to promote relevant research and patient registries.

Ways to Promote Relevant Research

The main barriers to conducting research that is relevant to the concerns of PIOs are physicians’ lack of awareness about PIOs’ concerns and the dearth of time and funds the physicians have to focus on research needs, which often pertain to rare diseases. PIOs can encourage relevant research by:

  • Linking up with a researcher knowledgeable about the science of the disease
  • Contacting U.S. scientists who may be interested in the research (as referred by foreign researchers working in the field, if necessary)
  • Appointing a scientific or medical director who is a researcher to the PIO’s board of directors
  • Associating with a local hospital to interest staff in the disease
  • Teaming up with local doctors to gain their interest and to help ensure that doctors and patients attend pertinent medical conferences
  • Partnering with a variety of organizations, including professional societies
  • osting an exhibit booth and participating in poster sessions at professional meetings and conferences
  • Encouraging states to offer a matching program for research funding
  • Encouraging the NIH to convene a workshop or conference on the specific disease topic.
The discussants highlighted the need for a better understanding of the NIH application, review, and funding process and for regular interaction with the NIH. They suggested that the NIH (a) organize a 2-day seminar, for both PIOs and researchers, on “how the NIH works”; (b) create a Webcast presentation about the NIH; and (c) establish a trans-NIH public interest organization.

Patient Registries

The discussants noted the following points regarding patient registries:

  • Registries are important.
  • Grants can be used to help establish a registry.
  • Ensuring patients’ privacy is essential.
  • Access to and ownership of registry data are relevant considerations for the follow-up of patients and should be addressed when establishing a registry.
  • Registries may include a tissue bank.
  • PIOs should retain access rights to patients’ tissue for future research and testing.

Several resources of potential interest to PIOs are:

  • A template for registries, created by the Alpha-1 Foundation and available to PIOs. Contact Mr. John Walsh at JWWalsh@alphaone.org or 305-567-9888.

  • The National Disease Research Interchange (NRDI), a center for collection, preservation, and distribution of tissues and organs for research. The NRDI is supported by the National Center for Research Resources, NIH. See the NIH Guide for Grants and Contracts, vol. 26, no. 18, May 30, 1997 NIH Guide.
  • The Genetic Alliance, a coalition of more than 600 organizations that seeks to improve health by integrating genetic advances into health care. Large umbrella organizations such as this may be useful to smaller PIOs addressing the same issues. Contact Genetic Alliance.
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Scientific Breakout Sessions

NHLBI staff presented four scientific talks in simultaneous breakout sessions. The participants could attend any of the sessions, which included brief question-and-answer periods.

Much Ado about Nearly Nothing: Nanotechnology in
Heart, Lung, Blood, and Sleep Research

Dr. Denis Buxton, Heart Research Program, Division of Heart and Vascular Diseases (DHVD), described Institute initiatives in the new and growing field of nanotechnology. The term nanotechnology refers to the engineering or creation of extremely small (nanoscale) devices—the “nearly nothing” in the title of Dr. Buxton’s presentation. Yes, there is “much ado” about this nearly nothing—at the NIH and elsewhere.

Through nanotechnology, scientists are producing many kinds of minute devices that can be used to perform different tasks and functions. These nanosized objects are extremely powerful, precisely because they are so small and can perform functions and tasks that cannot be done using larger objects. For example, certain changes in the DNA and proteins inside of cells can lead to disease. However, DNA and proteins exist on the nanoscale and are far too small to be manipulated in a controlled fashion using conventional tools. The nanodevices that scientists are creating today will be small enough to interact with DNA and proteins to prevent, diagnose, or treat disease. Scientists also are working on safe methods to introduce nanodevices into the body for use as nanomedicines.

In February 2003, the NHLBI convened a working group of experts in many fields to explore the promise of nanotechnology. The combined efforts of biologists, chemists, physicians, and biophysicists and of researchers in engineering, material science, and polymer science are needed to develop nanotechnology for medical applications.

The application of nanotechnology to heart, lung, blood, and sleep disorders and diseases is just beginning. Four areas in which nanomachines could have an immediate impact are:

  • Targeted therapeutics
  • Tissue engineering
  • Molecular imaging
  • Biosensors and diagnostics.

In targeted therapeutics, scientists could use nanodevices to deliver drugs to an exact area of the body where they are needed. For example, they could couple a nanoparticle to a drug that kills blood vessels and to a targeting sequence that binds to new blood vessels in order to specifically kill new blood vessels contributing to the development of atherosclerosis. They could also couple antibiotics to nanoparticles designed to seek out bacterial biofilms in the lungs of patients with airway disease. By being able to target areas of the body, scientists will be able to (a) prevent a drug from entering other areas where it is not needed and could harm other tissues, thereby reducing a drug’s potential toxicity and side effects, and (b) achieve longer lasting effects by delivering drugs, some of which are not absorbed well by the body, over time.

In tissue engineering, scientists are already using nanodevices to help build new tissues to replace damaged ones. Many heart, lung, and blood diseases lead to organ or tissue damage. Using nanotechnology, scientists may be able to create new, healthy tissue to replace damaged tissue; make better artificial veins, arteries, and heart valves; develop a scaffold for growing patches of heart tissue to repair damage from heart attacks; and grow artificial lung tissue.

In molecular imaging, scientists strive to create nanodevices that can identify diseases in the body. Scientists hope to use nanoparticles to bind to blood clots and to help make clots more visible by ultrasound. They also hope to make nanodevices that will bind to viruses, bacteria, or other signs of disease—to see exactly where problems are occurring in the body.

In the areas of biosensors and diagnostics, scientists could use nanodevices as implantable sensors to detect problems inside the body and to improve diagnosis of disease. Scientists are pursuing the development of a nanodevice known as a nanocantilever to diagnose heart attacks more rapidly and specifically.

Researchers are working to make nanoparticles and nanodevices safe. Compared with larger objects, nanoparticles have different properties and their performance will be harder to predict. And scientists will have to carefully evaluate the biosafety of nanodevices before they can be approved for internal use.

To foster the development of nanotechnology, the NHLBI has prepared an initiative to fund nanotechnology centers and is formulating another initiative to support innovative research grants in this area. Nanotechnology is also a component of the NIH Roadmap; the NIH will hold a workshop in spring 2004 to plan for NIH Centers of Nanotechnology.

Discussion

In response to questions, Dr. Buxton elaborated on the possibilities of nanotechnology. For example, nanotechnology might be used to (a) construct sensors that will allow doctors to detect hypoxia in patients with sleep disorders and (b) monitor cells transplanted by blood transfusion in patients with bone marrow diseases. Nanodevices will require a power source, but could remain in the body as long as the power can be maintained.

Patching Your Genes: Converting Gene Therapy’s
Promise to Practice

Dr. Sonia Skarlatos, Vascular Biology Research Program Director, DHVD, described the nature and potential of gene therapy for heart, lung, and blood diseases and disorders. The goal of gene therapy is to modify a person’s genotype (genetic makeup) to produce desired changes in the person’s phenotype (physical, biochemical, and physiological makeup). Each cell nucleus contains 23 pairs of chromosomes consisting of DNA. Similar to a file cabinet, a chromosome contains genes, or files. By “patching” genes, scientists could treat both hereditary and acquired diseases.

In general, gene therapy involves a gene, a vector, and a target. The scientist selects a gene, places it in a vector (delivery vehicle), and sends the vector to its target, the organ or tissue needing repair. Two types of gene therapy are possible:

  • Ex vivo gene therapy—a scientist takes cells from an individual, inserts a gene into the cells, and places the cells back into the same person’s body. The advantage of this approach is that it does not provoke an immune reaction, because the therapy uses a person’s own cells. The disadvantage is that treatment is formulated on an individual, case-by-case basis, and is very expensive.
  • In vivo gene therapy—a scientist places a gene into a vector and then inserts the vector into the body. The advantage of this approach is that it can be used for anyone and is not limited to one individual. The disadvantage is that it may elicit an immune response.
An ideal vector would target the appropriate cell or organ, allow for regulation of gene expression, have no or minimal toxicity (too much expression could be toxic), not elicit an immune response, and allow for production of large quantities of the gene. Two types of vectors are possible:
  • Viral vectors—such as adenovirus, adeno-associated virus (AAV), herpes viruses, retroviruses, and lentiviruses. The advantage of a viral vector is that it is already programmed to enter cells.
  • Nonviral vectors—such as plasmids (small, circular DNAs), a combination of liposome (a tiny sphere made of a lipid bilayer surrounding a liquid) and plasmid, and protein nanospheres (made of DNA attached to protein particles).

The vectors used most commonly are adenovirus and AAV. To create a viral vector, the researcher must delete the harmful DNA (that portion that causes infection and viral replication) and insert the transgene that codes for the therapeutic protein. Because the viral vector is then unable to replicate, the researcher must use a “packaging” cell line. This cell line has the DNA that is missing from the vector, but is required for replication. By placing the vector into the cell line, the researcher enables the vector to replicate and generate large quantities of the gene.

Safety is a primary concern with gene therapy. Theoretically, the risks of gene therapy include:

  • Insertional mutagenesis—in which the vector DNA inserts itself into a region of a chromosome, activating a cancer-causing gene or other harmful gene.
  • Recombination—in which the vector DNA becomes attached to DNA from a virus also in the host (e.g., a cold virus), causing the vector to become infectious again.
  • Germ-line gene transfer—in which the vector DNA inserts into an egg or sperm and can be passed to subsequent generations.
Researchers have already conducted hundreds of gene therapy studies, and only one death has occurred in the United States, which was caused by an immune response to an adenovirus vector. Two cases of leukemia arose in Europe, which were caused by insertional mutagenesis of a retrovirus vector.

The first gene therapy trial occurred in 1988. The peak year for gene therapy trials was 1999 (91 trials). The number of trials decreased slightly after the death in the United States and the two leukemia cases in Europe. In 2002, there were 51 gene therapy trials and, in 2003, 57 trials.

All treatment protocols involving gene therapy must undergo a rigorous approval process. The U.S. Food and Drug Administration (FDA) must approve U.S. protocols. Studies supported by the NHLBI must be reviewed by the NIH Recombinant Advisory Council, the NHLBI, and a Data and Safety Monitoring Board. This review includes site visits before the study is approved and after it begins. The institution where the gene therapy study will be conducted also must approve the trial—through its Institutional Review Board and Institutional Biosafety Committee.

The FDA requires long-term follow-up of patients. Patients must be seen annually for the first 5 years after treatment and must complete questionnaires annually for years 6 through 15.

Most gene therapy trials have been for cancer. Researchers are or soon will be addressing several heart, lung, and blood diseases and disorders in gene therapy trials. Preceding the trials is a sequence of research—genomic research, cellular research, and studies in animal models. The trials also are sequenced—phase I, phase II, and phase III. The objectives are specific for each research stage. Research that fails to fulfill the objectives at one stage does not progress to the next stage.

Three examples of gene therapy studies supported by the NHLBI are:

  • Gene therapy for hemophilia B, a blood disorder that affects 1 in 30,000 males. The treatment consists of infusion of clotting factor. Gene therapy in a dog model of hemophilia B resulted in expression of clotting factor for up to 5 years. Subsequently, scientists infused a vector into the liver portal vein of 12 patients, which resulted in a transient 12 percent expression of clotting factor in 1 of the patients. Unfortunately, expression eventually dropped back to zero.
  • Gene therapy to promote angiogenesis (growth of blood vessels) in the heart. Researchers are currently focusing on using an adenovirus vector to deliver the gene for vascular endothelial growth factor (VEGF). Previous use of the vector in a pig model of induced ischemia yielded promising results that led to the generation of new blood vessels.
  • Gene therapy for alpha-1 antitrypsin deficiency, which is caused by a defective gene for alpha antitrypsin (AAT) and which compromises a person’s defense against lung infection. The only effective treatment for this condition is Prolastin from pooled sera. Researchers have created an AAV vector containing the baboon form of the gene for AAT. They injected the vector into the muscle of baboons, where the gene for AAT is expressed and whence its product is carried by the blood into the lung. Injecting the vector directly into lung tissue is very difficult. The researchers foresee a treatment for humans in which patients would receive an injection of vector directly into an arm muscle, where the protein would be produced and then carried to the lung to accomplish the therapeutic goal.

To promote gene therapy research, the NHLBI is funding Programs of Excellence in Gene Therapy (PEGTs). The programs consist of national core centers that can produce vectors and offer training programs. The centers are intended to facilitate clinical trials of gene therapy.

As with new technologies in any field, gene therapy will evolve over time and experience setbacks. Many successes are likely as more resources and efforts are committed for the future.

Discussion

In response to a question, Dr. Skarlatos observed that gene therapy might be useful to correct the venous malformation and vessel overgrowth seen in Klippel-Trenaunay syndrome. She also noted that the time from identifying gene deficiencies to initiating gene therapy protocols could be years.

Scientific Body Building: Tissue Engineering the
Cardiovascular System

Dr. Martha Lundberg, Clinical and Molecular Medicine Program, DHVD, summarized the research challenges, the role of the federal government, and NHLBI and NIH efforts in tissue engineering, or “scientific body building.” Tissue engineering has been defined as “the regeneration of biological tissue through the use of cells, with the aid of supporting structures and/or biomolecules.”

Tissue engineering is a fast-emerging field of research that promises to offer new treatments and cures. This promise is of particular interest to the many patients with end-stage disease requiring transplantation of organs and blood cells that are in short supply; patients who are not eligible for transplants; and patients who are critically ill and have no other options for treatment. For all them, tissue engineering offers the potential of new and effective alternative treatments.

The research challenges are many. First, researchers must clarify how cells interact with one another. With this understanding, they will able to make biomaterial scaffolds on which to support or inhibit cell growth. The scaffolds must be elastic, durable, and strong, and they must degrade at controllable rates and into biocompatible materials. Providing a blood supply to nourish new tissue will also be essential.

Getting tissue-engineered products to the clinic is another major challenge. The products must have useful shelf lives, and procedures must be in place to ensure quality control at all stages of development. Industry will be called upon for testing, production, and preservation of products. The FDA has established an Office of Combination Products to handle the review and regulation of drug–device combinations, which includes tissue-engineered products.

The federal government has an important role in fostering tissue-engineering research to solve public health problems. The government is:

  • Coordinating resources for tissue engineering and regenerative medicine therapies
  • Supporting academia–industry partnerships and creating transagency collaborations to translate scientific advances into clinical practice
  • Sustaining research efforts and catalyzing science teams through multidisciplinary training
  • Supporting fundamental research in tissue engineering
  • Disseminating findings to the public.

Information on interagency activities related to tissue engineering is available at Tissue Engineering.

Two main activities at the NIH to promote research on tissue engineering are:

  • The NIH Bioengineering Consortium BECON.
  • The convening of two trans-NIH symposia, which enabled the research community to inform the NIH about the state of the science and to help guide the NIH research program. The symposia were entitled “Nanoscience and Nanotechnology: Shaping Biomedical Research,” held in June 2000, and “Reparative Medicine: Growing Tissues and Organs,” held in June 2001.

In addition, the NIH has issued several program announcements to encourage research on tissue engineering, including:

  • Functional Tissue Engineering for Heart, Vascular, Lung, Blood and Sleep Disorders and Diseases: SBIR/STTR Initiative PAR-01-006.
  • Bioengineering Research Grants PA-02-011.
  • Bioengineering Research Partnerships (BRPs) PAR-04-023.
A BRP is a multidisciplinary research team that combines bioengineering expertise with basic and/or clinical investigators. It must use an integrative, systems approach to develop knowledge and/or methods to prevent, detect, diagnose, or treat disease or to understand health and behavior. The NHLBI has funded 37 BRPs. In one, researchers are developing vascular shunts for patients being treated for peripheral vascular disease or receiving hemodialysis. Another research team is developing artificial arteries that expand and contract like natural arteries.

Discussion

In response to questions, Dr. Lundberg mentioned that tissue-engineered products could be compromised if a patient who is providing cells to be used in engineering tissue has a genetic problem. This limitation could potentially be overcome by using gene therapy.

The Cellular Jigsaw Puzzle: Putting It Together With
Genetics, Genomics, and Proteomics

Dr. Susan Old, Bioengineering and Genomic Applications Scientific Research Group Leader, DHVD, described the possibilities and approaches offered by genetics, genomics, and proteomics to complete the “jigsaw puzzle” of cell activity. The completed sequencing of the human genome, made possible by the NIH’s Human Genome Project, has created unprecedented opportunities for science. Today, researchers are moving forward to explore the expression and function of individual genes (genomics) and their protein products (proteomics).

This research has implications for greatly improved understanding of health and disease. All diseases have some genetic component. The genetic contribution can be significant in and of itself, as in cystic fibrosis—a single-gene disease—or complexly related to environmental factors, as in type II (adult-onset) diabetes mellitus or infectious diseases such as AIDS. By identifying the genes and their function(s), scientists may be able to improve diagnosis and devise targeted therapies (including gene therapy) for individuals with a disease. The possibility of “personalized medicine”—understanding each individual’s risk for disease, intervening to lessen the risk, and treating disease in a directed way when it arises—has enormous implications for medicine and health in the future.

Completion of the human genome sequence has shown us that all humans mostly share the same DNA. Yet, individuals can have dramatic genetic variation, as reflected in their phenotypes and, potentially, their health and disease. The spectrum of health and disease is dynamic and, at any one time, most individuals are in the middle of the spectrum. Through the process of gene discovery, scientists are beginning to explore the genetic variation of individuals along the spectrum.

Identifying the cause of single-gene diseases is relatively easy, compared with finding the cause(s) of complex disorders that involve multiple genes as well as environmental factors. Two approaches for “teasing out” genes and environmental factors are:

  • Targeted approach: In this approach, researchers often create an animal model by eliminating (“knocking out”) a gene implicated in a disease and examine the effects on the animal. This research has led, for example, to identification of a gene involved in the accumulation of fat in mice.
  • Genomics approach: This approach involves discovery of common gene variants in individuals with a disease, identifying common markers of variation, and linking the markers (linkage analysis) to the disease. Researchers can conduct entire genome-wide scans for linkage analysis. The NHLBI is using this approach to study hypertension in the Family Blood Pressure Program.

Microarray technology is a powerful tool for analyzing the dynamics of gene expression. Researchers across the United States can share microarray facilities supported by the NIH. Using this technology, they can:

  • Compare the expression patterns of different genes in normal and disease states—this approach is being used, for example, to gain a better understanding of development of hypertrophy of the heart over time.
  • Establish “biosignatures” in health and disease—changes in patterns may yield, for example, clues about the exposure to disease, prognosis, and type of pathogen.

NHLBI researchers are studying gene–environment interactions. An area of much investigation is pharmacogenetics—the individual’s response to drugs. A database from the NIH Pharmacogenetics Research Network, a nationwide collaborative research consortium, can be accessed at NIH Pharmacogenetics.

In addition, the NHLBI supports Programs for Genetic Applications (PGAs) in 11 centers across the United States. The PGA program fosters application of genetic and genomic research findings. Each center offers resources (e.g., biological products), information, research tools, and education for the research community.

Recently, the Institute established the NHLBI Proteomics Initiative to stimulate development of novel proteomic techniques and to facilitate interaction within multidisciplinary centers. Proteomics research is even more challenging than genetic or genomics research—the human genome contains approximately 30,000 genes, but an individual’s cell complement includes about 3 million proteins. Understanding the expression of these proteins and miscues in their expression is essential. Mass spectrometry and protein arrays are two tools researchers are using to compare proteins in normal and disease states.

A cell is a dynamic enterprise with many interactions within and outside the cell. Each pathway of action in the body is extremely complex and detailed, with molecular and cellular interactions at every level. Genetic, genomic, and proteomic studies to understand the interactions are necessarily dependent on bioinformatics and computational approaches and resources. Through the integration of “systems biology,” researchers can examine all elements, measure relationships, and perturb the system to understand and, eventually, predict reactions. By emphasizing new pathways of discovery, multidisciplinary research teams, and clinical applications, the NIH Roadmap is helping to chart this new course in medical research.

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Sleep and Its Disorders

The topic for the scientific presentation at the PIO meeting was sleep and its disorders. The NHLBI houses the National Center on Sleep Disorders Research (NCSDR). In March 2004, the NIH is holding a major meeting, Frontiers of Knowledge in Sleep and Sleep Disorders: Opportunities for Improving Health and Quality of Life, in Bethesda, Maryland. The meeting is sponsored by the NCSDR and the Trans-NIH Sleep Research Coordinating Committee. Several professional associations and PIOs are co-sponsors.

In his presentation, Dr. David White, Associate Professor of Medicine, Harvard Medical School, and Director, Sleep Disorders Program, Brigham and Women’s Hospital, addressed four topics:

  • Why do we sleep?
  • Physiological determinants of alertness and performance
  • Health effects of sleep deprivation<
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  • Sleep disorders.

He elaborated on these topics, giving examples from NIH-funded research.

Why Do We Sleep?

Dr. White noted that all species need sleep, but the reason why is not understood. Scientists have posited several theories over the years and, currently, are focusing on modulation in the brain’s neurochemistry. Studies of metabolic activity in the brain show that levels of adenosine increase during wakefulness and decrease during sleep. Because many of the studies have been done in cats, adenosine has been labeled the “cat-napping chemical.”

Physiological Determinants of Alertness and Performance

Researchers are learning about the physiological determinants of alertness and performance largely from studies of accidents (automobiles, trucks). The studies suggest four determinants:

  • Biological time of day (circadian phenomena)—increased wakefulness and performance relate to low melatonin levels, whereas sleepiness relates to high melatonin levels. The number of truck accidents is highest between 1 a.m. and 7 a.m., and they are related to driver fatigue.
  • Number of hours awake—studies of 32 hours of continuous wakefulness show a decrease in reaction time, cognitive throughput (on math tests), memory, and eyeblinks after 16 hours and an increase in rolling eye movements. The number of fatigue-related truck accidents after 13 hours of driving increases 16-fold.
  • Duration of nightly sleep—Having six or fewer hours of sleep at night is associated with decreased performance in a psychomotor vigilance task (computer use), and performance steadily deteriorates when sleep deprivation continues over weeks. Importantly, individuals do not recognize that they are impaired.
  • Sleep inertia (the time needed to wake up)—To become fully alert takes 1-2 hours; to perform adequate cognitive throughput takes 3 hours.

Health Effects of Sleep Deprivation

Sleep deprivation is common in the United States and has many consequences beyond falling asleep at meetings or having accidents. Dr. White noted that more research is needed to understand the neurocognitive effects of sleep deprivation. Studies demonstrate that humans need 7-8 hours of sleep each night and cannot maintain health or function effectively if deprived of sleep over time.

Studies in young men sleeping 4 hours a night for 6 nights show impaired glucose tolerance (requiring a 50-percent increase in insulin), decreased leptin levels (indicating increased hunger), increased levels of cortisol (stress hormone) in the evening, and increased sympathetic nervous system activity (higher blood pressure, heart rate). The Nurses’ Health Study showed an 80 percent increase in incidence of myocardial infarction (MI) among nurses receiving only 5 hours of sleep, as well as an increased incidence of MI among those sleeping 9 or more hours. Mice and rats that are totally deprived of sleep consume higher amounts of energy, and their fur deteriorates.

Sleep Disorders

Dr. White focused on two types of sleep disorders—excessive daytime sleepiness and insomnia.

Excessive daytime sleepiness, or hypersomnolence, is a sleep disorder and, as such, is different from fatigue. Hypersomnolence is caused by an increased sleep drive (e.g., in narcolepsy), sleep disruption (e.g., from obstructive sleep apnea, restless legs syndrome [RLS]), inadequate sleep (self-imposed or as a result of shift work) and other conditions (e.g., medications, depression). It is associated with decreased quality of life, a sixfold increase in automobile accidents, mild pulmonary hypertension, systolic hypertension, and arrhythmia. Some evidence indicates that hypersomnolence also is associated with an increased incidence of congestive heart failure, myocardial infarction, and stroke.

Narcolepsy is a disorder of the components of REM (rapid eye-movement) sleep and has various manifestations, including hypersomnolence. Researchers have only recently identified a possible cause of narcolepsy, and their findings point to degradation of the cells in the hypothalamus—a neurodegenerative process. Current treatment is based on the use of stimulants, such as Ritalin, dexadrin, and modafinil, which reduce the need for sleep.

Obstructive sleep apnea is very common, perhaps as common as asthma, and is characterized by a recurring decrease of oxygen in the blood, which stimulates brain activity and respiration, causing the individual to wake up. The major defect causing this disorder is an inadequate (anatomically small) upper airway, which is predisposed to collapse during sleep. Studies show that the disorder contributes to increased pulmonary hypertension and increased systolic hypertension. Current treatments include nasal devices and dental appliances. The efficacy of surgery, a relatively new approach, is not consistent.

Insomnia is defined as being unable to sleep 3-4 nights per week. This sleep disorder is increasingly common in the United States, and the prevalence of chronic insomnia is estimated at 10-17 percent of the population. The causes are many; they include depression, anxiety, neurological and medical factors, conditioned responses, irregular sleep schedules, and circadian disorders (e.g., with shift work).

Dr. White elaborated on conditioned insomnia, which stems from an acute, stressful event and is maintained chronically overtime by negative associations and anxiety as a person seeks to fall asleep. Behavioral approaches approaches—such as maintaining good sleep hygiene (e.g., reducing intake of caffeine), cognitive therapy, relaxation training, sleep restriction, and stimulus control—and hypnotics (benzodiazepines, sedatives) are used to treat chronic insomnia. Behavioral are successful in many cases. The many and growing number of hypnotics differ in dosage, half-life, and duration of action (some 1-2 hours, others 4-18 hours). Dr. White noted that use of hypnotics for chronic insomnia is extensive in Europe, where they are prescribed for 1-5 years, but more limited in the United States, where they are generally prescribed for less than 6 months. Use of sedatives is increasing in the United States.

Dr. White summarized his remarks as follows: (a) many individuals are not getting enough sleep; (b) the NIH is funding much research on sleep and sleep disorders, (c) researchers are making progress, and (d) much more information is needed.

Discussion

Dr. White said that the first signs or symptoms for consulting a physician about a possible sleep disorder are inability to sleep at night and excessive sleepiness during the day. In response to questions, he noted the following: (a) sleep apnea and other sleep disorders are often associated with lung diseases, such as asthma, emphysema, and COPD, and with heart disease, such as heart failure; (b) little is known about the short- or long-term effects of prednisone on sleep; (c) nothing is known about the neurobiology of idiopathic hypersomnia; (d) snoring may or may not be related to sleep apnea; and (e) ongoing studies of sleep deprivation among medical residents are expected to provide interesting data and to stimulate changes in practice.

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Participating in Research

Ms. Sheila Connolly, member of the Restless Legs Syndrome Foundation Advisory Council and the National Center on Sleep Disorders Research Advisory Board, shared her experiences of participating in clinical studies and discussed the process for volunteering and participating in a study. Ms. Connolly first became aware in 1989 that her “jumpy legs” were a defined medical disorder. A neighbor had read about RLS in literature from the National Organization of Rare Diseases (NORD).


Through initial contacts with NORD and with individuals suggested by NORD, Ms. Connolly began the grass-roots organization of the Restless Legs Syndrome Foundation. Through her physician, she identified a neurologist working in the field, who referred her to a researcher at Robert Wood Johnson Medical School and a potential benefactor. The researcher was conducting research on hereditofamilial RLS and became very interested in Ms. Connolly’s large, extended family, which included her five siblings, all of whom had RLS.

In 1990, Ms. Connolly began participating in a study as a volunteer. Although at first anxious and nervous, she came to realize that participation in a study can be:

  • “The beginning of a golden opportunity” to help solve the mystery of a disease that profoundly affects your life and the lives of others
  • A time of excitement, knowing that someone is trying to find answers to your condition
  • An opportunity to make a difference, if not in your lifetime, perhaps in the lifetimes of your children and grandchildren.

Ms. Connolly emphasized that “the thought of not participating never occurred to me” because of the number of family members affected by RLS. Still, the study was more involved and lengthier than she realized. Identifying genes that cause and contribute to disease is a long-term research effort. Many hours are consumed in reconstructing family trees, contacting family members, obtaining informed consent, interviewing and obtaining blood samples, updating information in follow-up, and maintaining family members’ commitment.

An individual volunteer is asked to:

  • Give informed consent after reviewing the research protocol
  • Participate in telephone interviews
  • Provide a medical history
  • Submit blood or tissue samples and other data (e.g., blood pressure, pulse readings)
  • Complete questionnaires
  • Notify research coordinators of changes in address or telephone numbers, for purposes of follow-up
  • Sign legal papers and inform legal next of kin to assure postmortem donation of tissue, if needed for the study and as agreed to by the volunteer.

A volunteer will provide information and samples at the beginning of a study and then on a continuing or follow-up basis as needed. Ms. Connolly noted that her family’s participation in the initial research led to participation in a collaborative study conducted in Canada and a study conducted by the National Institute on Aging, NIH. On her death, her brain and spinal tissue will be harvested and stored for further research purposes.

In conclusion, Ms. Connolly captured her experience as follows:

  • I have been in the right place at the right time
  • I learned how to advocate for myself and others with my disease
  • This research will one day offer a better understanding of the cause of my disease and provide improved treatment strategies
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  • This is an exciting time in the field of medical research
  • The information that patients provide cannot be underestimated
  • Patients and families interested in participating in clinical research need to have a positive, “I-can-do-it” attitude
  • Each person’s contribution makes a difference.
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Sharing Best Practices/Lessons Learned

PIO representatives facilitated six concurrent discussions, each on a specific topic. Facilitators shared their experiences and provided handout materials, and participants were encouraged to circulate among the discussion tables as they wished. Approximately 6 to 15 individuals contributed to the informal and interactive discussions at each table. The six topics were:

  • Developing materials for patients and the public
  • Fundraising
  • Organizing a scientific advisory board
  • Putting a face on disease
  • Starting a disease registry and mobilizing patient participation in research studies
  • br>
  • Starting and sustaining support groups.

The discussion at each table is summarized below.

Developing Materials for Patients and the Public

Facilitators—
Ms. Dolores O’Leary, Director, Sarcoid Networking Association
Ms. Amy Verstappen, President, Adult Congenital Heart Association

Ms. O’Leary and Ms. Verstappen shared their experiences in developing print and Web-based materials for patients and the public. They provided, as handouts, examples of their print materials—pamphlets about the PIOs, a double-fold business card with business information on the front and disease information inside, a newsletter, small cards with inspirational messages and PIO information, and small writing pads. Other handouts included information on the responsible management of a PIO’s Web-site message board and/or listserv.

Message boards and listservs where patients can exchange and discuss health-related information are a wonderful resource and source of support for patients. They also can be a powerful teaching tool and, if monitored carefully, a way to counter misinformation. PIOs should become knowledgeable about the computer resources available in order to share this information with patients.

Not everyone has access to a computer or online service. To reach all patients and constituencies, PIOs need to develop and disseminate print materials, as well as Web-based information.

In discussion, the participants suggested the following tips for print and Web-based materials.

Tips for Developing Print Materials

  • Create materials that are eye-catching—they do not have to be expensive and glossy.
  • Develop materials that are easy to understand—define all medical terms and write at the 5th to 8th grade level. If you wish, include material at a higher reading level on the same page or in the same document—use text boxes, for example, to enclose easier-to-read material.
  • Review and edit all materials—for errors of spelling or grammar and omissions of important information.
  • Make sure that medical and scientific experts (e.g., your scientific board) review all your materials for medical and scientific accuracy.

Tips for Reducing the Cost of Print Materials

  • Charge a small fee, on a sliding scale, to cover the costs of brochures.
  • Ask for donations from organizations—pharmaceutical companies often will help pay for materials, and you can have them agree to not make changes in the materials or to insert information.
  • Encourage physicians to contribute a personal donation when you give them materials.
  • Print brochures as part of an organized campaign and ask sponsors to donate to the campaign.
  • Partner with other organizations to get a reduced rate on printing.
  • Some printers print specific colors on certain days of the week, for ask for a better rate to print your color materials on the day they normally print the colors you need.
  • Investigate discounts on shipping (e.g., of bulk mailings).
Tips for Responsibly Maintaining Online Message Boards and Listservs
  • Avoid exchanging medical advice on your Web site—patients may be harmed and your PIO may be liable.
  • Build an online message board culture that discourages posters from asking for or giving medical advice. Educate list members to tell individuals posting messages that ask for advice to speak with their doctors.
  • Provide a disclaimer on your site stating that information on the message board reflects the opinion and experience of the individuals posting messages and should not be considered medical advice.
  • Become a member of your own listserv or message board in order to respond to misinformation, and encourage the medical experts on your advisory board to participate.
  • Assign someone to be the moderator of the message board and to read every posting. Have the moderator (a) contact individuals who post messages with inappropriate information and (b) correct postings containing misinformation by providing links to accurate scientific information already reviewed by the PIO’s scientific board.
  • Consider joining HonCode, an international not-for-profit organization that reviews sites containing health information. HonCode accredits sites that offer sound, responsible, medical information and that promote responsible Web practices. Contact HonCode at HonCode.
  • Do—establish clear policies for your forum; publish the policies and send them to each new registrant; assign a moderator with a Afirm, but gentle hand@ to read all postings, establish a helpful, positive tone with the forum participants, respond promptly to e-mails and messages, edit all postings that are not consistent with the policies and so inform the individual who posted the message; and encourage an appropriate level of anonymity.
  • Don’t—allow commercial ads or other solicitations; let anyone offer medical advice; allow conversations “off topic”; or allow unauthorized “spam.”
  • If you do not have a message board or listserv, partner with related organizations that have credible, monitored listservs and refer people to those sites.

Tips for Helping Patients Gain Access to Computers

  • Encourage patients to check their local library or senior citizen center (many libraries and centers provide Internet access) and to ask neighbors and friends about using their computers.
  • Ask computer companies, schools, and universities to donate computers for patients’ use.
  • Ask companies to provide in-kind or other donations to defray monthly Internet fees for patients who cannot afford them.
  • Prepare a PowerPoint presentation featuring your Web site materials to use for community presentations and distribute to interested individuals.

Tips for Designing a Web Page

  • Keep it simple—the information provided is the most important part of your Web site.
  • Ask members of your PIO who have skills in Web design to help develop your site.
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Fundraising

Facilitators—
Ms. Anne Garrett, Executive Director, Preeclampsia Foundation
Ms. Sue Byrnes, Executive Director, LAM Foundation.

Ms. Garrett and Ms. Byrnes facilitated separate discussions at adjacent tables. For handouts, they provided booklets, compact discs, and other materials used in fundraising.

Some tips for raising and using funds and other support are:

  • Develop a strategy for approaching potential donors.
  • In letters and brochures, state your mission, goals, objectives, costs, and other related information and highlight progress made.
  • In direct-mail correspondence, announce new developments (e.g., a new diagnostic test) and ask for donations.
  • On your membership form, note that contributions to nonprofit organizations are tax deductible and include an option for contributing extra donations or gifts.
  • When corresponding with universities, note that they can use endowment funds for your worthy cause—to find a cure for a disease.
  • Communicate regularly and often by telephone, letter, and e-mail.
  • Identify prominent individuals by searching the Lexis-Nexis Web site (www.lexisnexis.com), and write letters to them asking for advice on fundraising—do not ask specifically for money.
  • Involve patients and their families.
  • Hold fundraising conferences and involve patients= families.
  • Solicit donations from patients on a registry and invite them to fundraising events.
  • Encourage volunteerism among your members and allow patients' families to become involved—they may develop their own fundraising programs.
  • Search your database of members for those who have not donated recently, and send reminders to them to encourage donations.
  • Donate items to auctions, including Internet auctions (e.g., Ebay),to raise funds.
  • Encourage donors to contribute more than they did in the past—your costs and the costs of research increase every year. Let donors know the costs of a specific project.
  • Watch your manners. Address individuals by their correct names, remember details about patients, be warmly communicative and smile, send thank-you notes, and treat people well.
  • Thank everyone for his or her donation, no matter what the size. Most of the funds that support PIOs come from individuals, not corporations or celebrities.
  • Do not fear rejection—no one receives money if they don’t ask.
  • Never take “no” for an answer. For most potential donors, “no” means “not now.” Be respectful and try again later or in a different way.
  • Contract with professional fundraisers—a good option for smaller PIOs that do not have the time or staff for systematic fundraising. Contracted fundraisers receive a percentage of the donations. Beware of predators that could destroy your credibility.
  • Be accountable for the funds and donations given to you.
  • Avoid funding pet projects. Maintain a diverse medical and scientific board.
  • Piggyback meetings to reduce expenses.
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Organizing a Scientific Advisory Board
Facilitators—
Ms. Betsy Peterson, Founder, Children=s Heart Foundation
Ms. Judy Simpson, Founding President and Board Member Emeritus, Pulmonary Hypertension Association


Ms. Peterson and Ms. Simpson counseled the participants individually. A handout, entitled “Organizing a Scientific Advisory Board,” summarized the steps that the Children’s Heart Foundation took to form its Medical Advisory Board. The handout describes the mission of the Children’s Heart Foundation and elaborates on the board—its purpose, formation, duties and responsibilities, and diversity. A copy of the handout may be obtained from Ms. Peterson at 847-441-1709 or chfBetsy@aol.com.

Copies of the Pulmonary Hypertension Association’s journal, Advances in Pulmonary Hypertension, also were distributed. The journal is available on the association’s Web site: Pulmonary Hypertension Association.

Some tips for organizing a scientific advisory board are:

  • First, secure the support of a physician you know.
  • Enlist his or her help in identifying and contacting other doctors and researchers in the field who might be interested in your cause.
  • Ask patients for the names of their doctors.
  • Seek to bring together a diverse group of world-renowned physicians who would give your organization credibility.
  • Develop a document describing the duties and responsibilities of the board—for example, reviewing grants, participating in annual meetings, sharing information about the PIO with patients, attending fundraising events, financially supporting the PIO. Specify your expectations (e.g., support of the PIO’s mission) and the duration of board terms.
  • Follow up initial contacts with a letter and information about your PIO.
  • Nurture and give direction to the board.
  • Guard against conflict of interest in the awarding of grant funds—for example, obtain “outside” peer review for applications from board members, or do not allow members to submit applications for research support while they are serving on the board.
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Putting a Face on Disease

Facilitators—
Ms. Wendy Chaite, Executive Director, Lymphatic Research Foundation
Mr. Robert Gelenter, Mended Hearts Inc.

Ms. Chaite and Mr. Gelenter noted that putting a “face” on a disease—to make it visible and identifiable to the public—can be difficult when the disease is very rare or when a disease has many faces (e.g., sarcoidosis). Diseases that cause an obvious physical deformity (e.g., lymphedema) are easier for the public to appreciate and to give support to.

Some tips for putting a face on disease are:

  • Identify celebrities, who can be very helpful in publicizing a disease,and ask for their help.
  • Understand that diseases such as COPD present a special challenge because the public may perceive them as self-inflicted.
  • Consider portraying different faces for your disease to different audiences (e.g., legislators, researchers, financial contributors).
  • Build your disease onto a broader platform of health care and medical research, as needed.
  • Adopt a “positive spin”—for example, “it's great to be alive and to help others” (the Mended Hearts motto
  • Use a photograph of a patient at his or her best and worst—to convey to doctors, patients, and families the vigor that might be restored through research.
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Starting a Disease Registry and Mobilizing Patient Participation
in Research Studies

Facilitators—
Ms. Shelly Bowen, President, Barth Syndrome Foundation, Inc.
Ms. Donna Appell, President and Founder, Hermansky-Pudlak Syndrome Network, Inc.

Ms. Bowen and Ms. Appell provided several handouts. Two pertained to disease registries, listing the benefits, potential pitfalls, and general guidelines for a disease registry and clinical database and describing the Genetic Alliance Biobank clinical data registry. Two other handouts gave suggestions for recruiting families for clinical trials and listed the benefits, potential pitfalls, and general guidelines for recruiting patients for research.

Ms. Bowen described the experience of the Barth Syndrome Foundation in establishing a disease registry. She suggested two examples of good registries—the Pediatric Cardiomyopathy Registry and the International Registry of Holoprosencephaly and Brain Development. Ms. Appell commented that she has a brief slide show to inform families about participating in research. Contact her at 516-922-3440 or Appell@worldnet.att.net.

In discussion, the participants suggested the following tips for starting a disease registry and mobilizing patients for research studies.

Starting a Disease Registry

  • A patient’s socioeconomic status may affect his or her ability to participate.
  • Paid outreach may be needed to recruit patients who have been identified as potential participants in a registry.
  • Smaller or new PIOs may want to partner with an umbrella organization, such as the Genetic Alliance.
  • Examine the ownership of the registry and ensure that your PIO’s current and future needs are protected.
  • Information may be more difficult to obtain for diseases that are classified as “nonreportable” (reporting is not mandated by the federal government or state governments).
  • Consider privacy issues and the requirements of institutional review boards (IRBs) when accessing and using patient records, including health records.
Mobilizing Patient Participation in Research Studies

The participants addressed seven topics: IRBs, informed consent, privacy considerations, collection of data, recruitment of patients, barriers to participation, and building the public’s trust.

Institutional Review Boards

  • Determine how IRB requirements will apply to the project and your PIO. Obtaining IRB approval may be a major barrier for some PIOs.
  • Consider contracting with an independent IRB company or arrange for the organization managing the study to obtain IRB approval.
  • For registries or studies involving multiple locations, each site’s IRB will likely want to conduct a review.
  • A good source for IRB information is the Office for Human Resource Protections, DHHS.

Informed Consent

  • Good examples of consent forms are available. Contact your IRB for more information.
  • Ensure that the consent form addresses the plans for sharing participants’ data currently and in the future, as well as the plans for follow-up studies.
  • When obtaining informed consent, follow the mandatory IRB elements and:
  • Know the study protocol
  • Discuss the risks and benefits
  • Understand the belief system of the patients (e.g., cultural and religious beliefs)
  • Consider the special needs of patients (e.g., large-print consent forms for patients with diminished sight, translated forms for patients speaking other languages).

Privacy Considerations

  • Determine how the Health Insurance Portability and Accountability Act (HIPAA) applies to your PIO. Information on the HIPPA Privacy Rule is available.
  • Consider patient confidentiality issues.

Collection of Data

  • Consider the burden on patients and delete unnecessary questions.
  • Identify critical data items and standard questions that all patients will be asked.
  • In structuring a database, anticipate the need for expandable responses (e.g., from relatives with the disease) and for skip patterns that allow patients to skip irrelevant questions.
  • Consider conducting an annual follow-up of patients (in accordance with IRB requirements).
  • Consider the possibility of collecting data using a Web-based system.
Recruitment of Patients
  • Staff a 24-hour telephone hotline for patients.
  • Register your PIO in community directories.
  • Promote articles and stories about your PIO and patients in local newspapers and on television.
  • Provide articles to hospital and support-group newsletters.
  • Identify and establish a connection with the “entry point” for your disease—develop a relationship with the physician diagnosing the most cases of the disease or ask a research center to establish a center of excellence for research on the disease.
  • Use telephone calls and letters—they are more effective recruiting tools, because they are more personal than e-mail.
  • Understand that response rates will vary.
  • Invite patients to register on your PIO’s Web site.
  • Hold conferences and advertise them widely to attract patients and doctors.
  • Ask physicians to refer their patients to your PIO.
  • Remember that many families do not have access to the Internet.

Barriers to Participation

Potential barriers include:

  • Difficulty in finding a sufficient number of patients with the disease.
  • Needing to confirm a patient’s diagnosis.
  • Patient failure to maintain contact with the study and PIO.
  • Patient perceptions that the risks outweigh the benefits of participation—participation may depend on the invasiveness of the research and the availability of experimental treatments. Patients who are mildly afflicted with disease may not be willing to participate because they perceive that the risk of adverse events is greater than the potential benefits. Patients are reluctant to participate if they perceive that they may be assigned to the control arm of the study.
  • Delays in implementing the study and poorly timed recruitment of patients.
  • Cultural attitudes, language difficulties, and education that do not support participation.
  • Public’s lack of trust in medical research.

Building the Public’s Trust

Public trust can be fostered by:

  • Strengthening the PIOs and their relationship with the NIH
  • Encouraging PIOs to reach out beyond their disease focus to other, related diseases and groups
  • Improving communication between physicians and patients (e.g., simplifying disease terminology for patients).


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    Starting and Sustaining Support Groups

    Facilitators—
    Dr. Eddie Glenn, Founder, Sarcoidosis of the Midlands of South Carolina
    Ms. Barbara Cady, Board Member, Take Off Pounds Sensibly (TOPS) Club

    Dr. Glenn and Ms. Cady shared their thoughts on starting and sustaining support groups. The discussants agreed that support groups are important—they give patients the opportunity to talk with others, find new ways to cope with their disease, and know that they are not alone. Support groups can extend the benefits for patients by including caregivers, families, and health care professionals in the group and by encouraging all members to share their experiences, knowledge, and feelings.

    Support groups may be organized by PIOs or be independent groups. They may be local entities or part of a national network, and they may be based on or maintained by telephone contact, Web-based communications, and face-to-face interactions. Each group is different, and each group will change over time as its members and goals change.

    Although the best interactions are face-to-face, online groups offer an attractive, alternative forum for support. Online interactions may be the main support for patients with rare diseases who are distributed throughout the United States and the world and for patients who are unable to travel easily. Through online groups, patients can access a wide network of medical resources and information on all aspects of their disease—symptoms, testing, treatment, and research—and can exchange information and experiences with others throughout the world. Patients should look for a friendly and helpful group, carefully weigh the accuracy of any medical information provided, and consider their own concerns about privacy.

    Some tips for starting and sustaining a support group are listed below.

    Starting a Support Group

    • First, define your mission and purpose
    • Determine your goals
    • Identify your patients and constituents
    • Develop a simple survey to ascertain the needs and wants of potential members
    • Decide on appropriate (including age-appropriate) activities
    • Define the nature of support that the group will provide—telephone, e-mail, and/or face-to-face contact
    • Be sensitive to cultural and ethnic issues when reaching out to members and the public.

    Sustaining a Support Group

  • Starting a group is not difficult, but sustaining a group is—yet it can be done.
  • Maintain the focus of the group—it is too easy to become only a social group.
  • Share leadership roles and maintain fluidity—have facilitators serve on a rotating basis.
  • Enlist volunteers—one person cannot do it all.
  • Hold group meetings in a location that is accessible and comfortable.
  • Schedule meetings at suitable times—not during holidays, vacation months (summer), or periods of inclement weather.
  • Stay in touch through e-mails and telephone calls during the months when the group does not meet. Study other support group models and draw on their strategies for success—for example, family counseling, 12-step programs.
  • Remember that the support group is a collection of individuals with different needs.
  • Try to have face-to-face “buddy days” once a month—it takes only two people to have a meeting.
  • Buddy up newer members with older members.
  • Keep the group fresh and energized—avoid becoming bogged down by patient complaints about their disease.
  • Alternate the content of meetings—share stories at one meeting, listen to an expert’s presentation at another.
  • Reinvent the group as needed—assess its accomplishments each year relative to its goals and changing membership.
  • Remain sensitive to the cultural and ethnic diversity of the group’s members.
  • Address patients’ needs locally—especially if the support group is part of a national network.
  • Hold retreats and reunions for group members—as possible within the physical and financial limitations of the members.
  • Host mini-regional conferences and meetings of related support groups.
  • Hold an annual conference of researchers and patients—this can be a wonderfully dynamic experience.
  • Reach out to and visit local hospitals, research laboratories, and drug manufacturers—to help researchers and health care professionals understand the problems patients face.
  • Consider structuring a “turn-key” approach for expanding local groups within a national network. TOPS has a “turn-key” kit available for sustaining a national network of local groups. Contact Ms. Cady at 304-363-3510 or BCady290@aol.com.


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    Closing Remarks

    Dr. Alving thanked the PIO representatives and the NHLBI staff for their contributions and participation.

    The meeting was adjourned at 4:30 p.m.

    Modified 7/12/04
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